Abstract 2015: BRCA1 expression and genomic aberrations in triple negative breast tumors.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Among breast cancer tumors, a group named as triple-negative breast cancer (TNBC) which do not express hormone receptors and HER2 (ER-, PR-, HER2-) do not have specific therapy. Therefore, knowing the genes involved in this type of tumor is highly relevant for treatment. Intense research in these tumors has been performed in order to identify new targets. We studied 48 TNBC tumors from Chilean patients by different approaches. In these tumors, we determined the expression, by immunohistochemistry, the different cytokeratins (CK5, CK14, and CK8/18) and EGFR. In addition, we analyzed BRCA1 expression and localization by immunohistochemistry. Using array-CGH, we characterized the genomic aberrations, in order to identify common alterations between tumors. A 62.5% (30/48) of the tumors were classified as basal-like. Expression and localization of BRCA1 analysis revealed that a 22.9% (11/48) of tumors presented normal expression of nuclear BRCA1, a 29.2% (14/48) has low or absent nuclear expression and a 47.9% (23/48) has altered BRCA1 localization, in addition to low expression in some cases. This suggests that the loss of expression of BRCA1 or its altered localization may be relevant for tumor progression. Analysis of genomic alterations by array-CGH revealed regions of gain (4p16.3-p16.2, 7p22.3-p22.2, 11p15.5, 19p13.3) and deleted regions (1q21.1, 6p11.2; 11q22.3) shared by more than 30% of these tumors. By grouping these tumors we identified three main groups, one of which correlates with the low expression / miss-localization of BRCA1. An analysis of the genes contained in these regions can determine the signaling pathways relevant to the progression of breast cancer. In this regard, by clustering, we identified a group of TNBC tumors (17/48) with amplification of AKT1, which may be relevant as a therapeutic target. FONDECYT 1080595, CONICYT 24091058. Citation Format: Teresa Tapia, Andres Aravena, Carolina Alvarez, Valeria Cornejo, Wanda Fernandez, Mauricio Camus, Alejandro Maass, Pilar Carvallo. BRCA1 expression and genomic aberrations in triple negative breast tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2015. doi:10.1158/1538-7445.AM2013-2015